埃博拉病毒病：病原体相关分子模式限制的Toll样受体3激动剂瑞他莫德在体内提供的保护作用及其作用机制

Ebola virus disease: In vivo protection provided by the PAMP restricted TLR3 agonist rintatolimod and its mechanism of action.

作者信息

Corona Angela, Strayer David, Distinto Simona, Daino Gian Luca, Paulis Annalaura, Tramontano Enzo, Mitchell William M

机构信息

Department of Life and Environmental Sciences, University of Cagliari, 09042, Monserrato, Italy.

AIM ImmunoTech, Ocala, FL, 34473, USA.

出版信息

Antiviral Res. 2023 Apr;212:105554. doi: 10.1016/j.antiviral.2023.105554. Epub 2023 Feb 16.

DOI:10.1016/j.antiviral.2023.105554

PMID:36804324

Abstract

Ebola virus (EBOV) is a highly infectious and lethal pathogen responsible for sporadic self-limiting clusters of Ebola virus disease (EVD) in Central Africa capable of reaching epidemic status. 100% protection from lethal EBOV-Zaire in Balb/c mice was achieved by rintatolimod (Ampligen) at the well tolerated human clinical dose of 6 mg/kg. The data indicate that the mechanism of action is rintatolimod's dual ability to act as both a competitive decoy for the IID domain of VP35 blocking viral dsRNA sequestration and as a pathogen-associated molecular pattern (PAMP) restricted agonist for direct TLR3 activation but lacking RIG-1-like cytosolic helicase agonist properties. These data show promise for rintatolimod as a prophylactic therapy against human Ebola outbreaks.

摘要

埃博拉病毒（EBOV）是一种极具传染性和致命性的病原体，可导致中非地区出现偶发性自限性埃博拉病毒病（EVD）聚集性病例，并有可能发展为疫情。在Balb/c小鼠中，以6mg/kg的人体耐受临床剂量使用rintatolimod（Ampligen）可实现对致死性埃博拉病毒扎伊尔株的100%保护。数据表明，其作用机制是rintatolimod具有双重能力，既作为VP35 IID结构域的竞争性诱饵，阻止病毒双链RNA的隔离，又作为病原体相关分子模式（PAMP）受限激动剂，直接激活TLR3，但缺乏RIG-1样胞质解旋酶激动剂特性。这些数据表明rintatolimod作为预防人类埃博拉疫情的治疗方法具有前景。